Cambridge Healthtech Institute’s Fourth Annual Protein-Device Combinations conference will cover the latest trends and challenges in integrating protein formulations with parenteral and alternative administration devices. In addition to focusing on parenterals, non-invasive and alternative routes for delivery will also be discussed. Specific considerations for formulating protein delivery systems so they maintain their stability and remain within their efficacious and safe target doses will be discussed. The meeting will feature in-depth case studies and discussions on the design and development of protein-device combinations that are safe and effective, compliant and commercially successful.

Join colleagues from around the world in this discussion of the key challenges and solutions in protein-device combinations development, and see how experts like you are integrating protein formulations with parenteral and alternative administration devices.

Commonly, “rules” for formulation and process design include the “command” to freeze dry below the Tg’ to insure product quality. Moreover, formulations should have very high Tg’s to insure good storage stability. These “rules” mean that more than trace levels of amorphous low Tg solutes or electrolytes should be avoided. However, recent data indicate that these rules can often be relaxed greatly without damage to critical quality attributes.

9:00 FDA Regulatory Requirements and Guidance for the Development and Marketing of Prefilled Syringes and Advanced Drug Delivery Devices

This presentation will consider recently issued FDA regulations and guidance for the development and marketing of drug delivery devices which are either indicated for, or co- packaged or prefilled with drugs and biological products. It will include good manufacturing practices, scientific and engineering information to be included in marketing applications and the reporting of manufacturing and design changes to approved applications.

The blood brain barrier (BBB) poses a formidable challenge for delivery of biologics to the central nervous system. Current clinical approaches for brain disorders bypass the systemic delivery route in favor of brute-force approaches such as intra-cerebral catheters and drug releasing implants. I will discuss our work on targeting the paracellular route of the brain microvascular capillary vessels that facilitates the delivery of systemically introduced biologics through the BBB.

Advances in formulation technology have allowed biologics to be formulated at ever higher concentrations, where viscosity becomes limiting, often necessitating large bore needles or longer injection times. Needle-free injection can resolve those issues by delivering viscous formulations in a fraction of a second, while providing market advantages via product differentiation. The impact of needle-free injection on protein activity and integrity following administration is evaluated at both aqueous and elevated viscosities.

11:45 A New Technology for High Volume/High Viscosity Biologics

Michael D. Hooven, President and CEO, Enable Injections, LLC

A new wearable Bolus Injector technology for subcutaneous delivery of high-volume/high-viscosity biologics has been developed that utilizes standard vial container closure. The system uses simple mechanical means to deliver 20+cc of high viscosity fluid with automated mixing of two vials and point-of-delivery dose adjustment. The unique power supply allows for very high pressures to be achieved, allowing rapid delivery though a 29-33g needle.

12:15 pm The Importance of Considering All Aspects of an Integrated Delivery System to Help Optimize Patient Outcomes

Optimal outcomes can only be achieved when all aspects of drug delivery are considered as an integrated system. The four key elements are the drug molecule, the primary container, the delivery device and the patient. For any treatment to be effective these elements have to work in harmony. This presentation will highlight the importance of this approach, with examples of systems designed to optimize the patient experience.

This talk describes the use of the inhalation route for delivery of proteins and peptides. Patient preference for inhalers over injections may lead to greater compliance and thus improved outcomes translating into a pharmacoeconomic benefit. The pitfalls and opportunities to develop an inhaled protein product will be summarized. Molecular optimization, formulation development, and device selection are essential factors when developing an inhaled product. Case studies, including in vitro and in vivo data, will be shared.

2:35 Oral Inhalation as a Delivery Option for Protein and Peptide Drugs

Almost all protein and peptide drugs are delivered by injection. Unfortunately, this invasive route of administration is a barrier to initiation of therapy and a hindrance to compliance once therapy has started. As an alternative, the oral inhalation route, integrating protein/peptide formulations with simple inhalers, provides a viable delivery option. The development of these non-invasive, patient-friendly combination products will be discussed.

A totally implantable miniaturuzed biosensor is being developed by our group for metabolic monitoring. This device utilizes immobilized enzymes for monitoring glucose and other metabolites. To prevent the foreign body response to the implanted sensor, we have developed a biocompatible coating that releases drug, (dexamethasone) and other tissue response modifiers (such as VEGF (vascular endothelial growth factor) and PDGF (platelet-derived growth factor). This presentation will focus on the biocompatible coating as well as the biosensor composition and functionality.

Lyophilization in pre-filled devices is a growing interest in the field of parenteral lyophilized products. The behavior during processing is influenced by the unique geometry and construction of the containers. In these studies, the sublimation rate and finished product attributes of model systems where evaluated in plastic syringes and glass cartridges. The studies show a direct comparison of the effects of the heat transfer characteristics of plastic versus glass syringes /cartridges. The processing data and finished product attributes will be presented.

This presentation will discuss our work on slow release formulations of proteins for ocular delivery. Formulations are prepared by first spray-drying followed by hot melt extrusion to produce a slow release formulation for proteins.